title: Evidence for the involvement of GPR40 and NADPH oxidase in palmitic acid-induced superoxide production and insulin secretion.
abstract: G protein coupled receptor 40 (GPR40) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex have been shown to be involved in the fatty acid amplification of glucose-stimulated insulin secretion (GSIS). The effect of palmitic acid on superoxide production and insulin secretion by INS-1E cells and the possible involvement of GPR40 and NADPH oxidase in these processes were examined in this study. Cells were incubated during 1 h with palmitic acid in low and high glucose concentrations, a GPR40 agonist (GW9508) and inhibitors of NADPH oxidase (diphenyleneiodonium, DPI) and PKC (calphostin C). GW9508 induced superoxide production at 2.8 and 5.6 mM glucose concentrations and stimulated insulin secretion at 16.7 mM glucose concentration involving both PKC and NADPH oxidase activation. Palmitic acid induced superoxide production through NADPH oxidase and GPR40-dependent pathways and the stimulation of insulin secretion in the presence of a high glucose concentration was reduced by knockdown of GPR40 using siRNA. Our results suggest that palmitic acid induces superoxide production and potentiates GSIS through NADPH oxidase and GPR40 pathways in pancreatic ? cells.
authors.affiliation: Department of Physiology and Biophysics; Institute of Biomedical Sciences; University of São Paulo (USP); São Paulo, SP Brazil.
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Graciano
authors.forename: Maíra Mello
authors.initials: MM
authors.lastname: Valle
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
authors.forename: Angelo Rafael
authors.initials: AR
authors.lastname: Carpinelli
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008744:Methylamines / Q000494:pharmacology; D051379:Mice; D019255:NADPH Oxidases / Q000502:physiology*; D009281:Naphthalenes / Q000494:pharmacology; D009861:Onium Compounds / Q000494:pharmacology; D019308:Palmitic Acid / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism*
chemical_list: C473036:Ffar1 protein, mouse; C515630:GW9508; D007328:Insulin; D008744:Methylamines; D009281:Naphthalenes; D009861:Onium Compounds; D011422:Propionates; D043562:Receptors, G-Protein-Coupled; D013481:Superoxides; D019308:Palmitic Acid; C007517:diphenyleneiodonium; D019255:NADPH Oxidases; C058819:calphostin C
keywords: fatty acid; palmitic acid; pancreatic beta cell; pancreatic islet; reactive oxygen species